Source:http://linkedlifedata.com/resource/pubmed/id/14592437
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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0014264,
umls-concept:C0017262,
umls-concept:C0026473,
umls-concept:C0030705,
umls-concept:C0041904,
umls-concept:C0086418,
umls-concept:C0162493,
umls-concept:C0185117,
umls-concept:C0205409,
umls-concept:C0439831,
umls-concept:C0805586,
umls-concept:C1334136,
umls-concept:C1708449,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2003-10-31
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pubmed:abstractText |
The exposure of human monocytes to the gram-negative endotoxin LPS provokes them to enter a transient state in which they are refractory to further stimulation by LPS. This phenomenon is known as 'endotoxin tolerance' (ET) and it is characterized by a decrease in leukocyte proinflammatory cytokine production in response to LPS. In the present study, we have analyzed the expression of IRAK-M mRNA and protein in a human model of ET using human monocytes isolated from peripheral blood. In these monocyte cultures, IRAK-M mRNA was expressed 6h after stimulation with different doses of LPS. However, endotoxin pretreatment induced a more immediate up-regulation of IRAK-M gene expression, transcripts appearing only one hour after a second LPS-challenge, and the production of high levels of IRAK-M protein in these tolerant monocytes. We also analyzed the response of monocytes isolated from septic patients within a temporal tolerance timeframe when stimulated ex vivo with LPS. In contrast to monocytes from healthy volunteers and patients outside of the tolerance timeframe, monocytes from septic patients rapidly expressed IRAK-M mRNA when stimulated with LPS ex vivo. Moreover, the expression of IRAK-M mRNA was more rapidly induced in the presence of a PI3K inhibitor, suggesting a connection between these two kinases. Thus, our data indicate that IRAK-M could play a pivotal role in the process of ET in human monocytes and provide evidence that PI3K is involved in regulating its expression.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Endotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/IRAK3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1 Receptor-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-291X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
311
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
465-72
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14592437-Cells, Cultured,
pubmed-meshheading:14592437-Dose-Response Relationship, Drug,
pubmed-meshheading:14592437-Drug Tolerance,
pubmed-meshheading:14592437-Endotoxins,
pubmed-meshheading:14592437-Gene Expression Regulation,
pubmed-meshheading:14592437-Humans,
pubmed-meshheading:14592437-Interleukin-1 Receptor-Associated Kinases,
pubmed-meshheading:14592437-Leukocytes, Mononuclear,
pubmed-meshheading:14592437-Lipopolysaccharides,
pubmed-meshheading:14592437-Middle Aged,
pubmed-meshheading:14592437-Protein Kinases,
pubmed-meshheading:14592437-Sepsis,
pubmed-meshheading:14592437-Up-Regulation
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pubmed:year |
2003
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pubmed:articleTitle |
Rapid up-regulation of IRAK-M expression following a second endotoxin challenge in human monocytes and in monocytes isolated from septic patients.
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pubmed:affiliation |
Research Unit, Department of Surgical Research, La Paz Hospital, Madrid 28046, Spain.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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